1ISH

Crystal Structure Analysis of BST-1/CD157 complexed with ethenoNADP

1ISH の概要

• エントリーDOI: 10.2210/pdb1ish/pdb
• 関連するPDBエントリー: 1ISF 1ISG 1ISI 1ISJ 1ISM
• 分子名称: bone marrow stromal cell antigen 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ETHENO-NADP, ... (4 entities in total)
• 機能のキーワード: adp ribosyl cyclase, nad glycohydrolase, cns, ethenonadp, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 62519.80

構造登録者

Yamamoto-Katayama, S.,Ariyoshi, M.,Ishihara, K.,Hirano, T.,Jingami, H.,Morikawa, K. (登録日: 2001-12-05, 公開日: 2002-03-13, 最終更新日: 2024-11-06)

主引用文献

Yamamoto-Katayama, S.,Ariyoshi, M.,Ishihara, K.,Hirano, T.,Jingami, H.,Morikawa, K.
Crystallographic studies on human BST-1/CD157 with ADP-ribosyl cyclase and NAD glycohydrolase activities.
J.Mol.Biol., 316:711-723, 2002

PubMed Abstract: cADPR is the novel second messenger that elicits calcium release from intracellular calcium stores and works independently of IP(3). In mammals, the ADP-ribosyl cyclase function is found in two membrane proteins, CD38 and BST-1/CD157. These enzymes, exposed extracellularly, bear cADPR hydrolase and NAD glycohydrolase activities. In spite of its functional importance, the structural basis of these enzymatic reactions remains elusive. We determined the crystal structures of the extracellular region of human BST-1 at atomic resolution in the free form and in complexes with five substrate analogues: nicotinamide, NMN, ATPgammaS, ethenoNADP, and ethenoNAD. The three-dimensional structural views of the reaction centre with these ligands revealed the mode of substrate binding and the catalytic mechanism of the multifunctional enzymatic reactions. In each catalytic cleft of the dimeric enzyme, substrates are recognized predominantly through van der Waals interactions with two tryptophan residues, and thereby the N-glycosidic bond of NAD is correctly exposed near a catalytic glutamate residue. Its carboxyl side-chain stabilizes the catalytic intermediate of the S(N)-1 type reaction. This conformation of the catalytic cleft also implies the mechanism of cyclization between the adenine base and the ribose. The three key residues are invariant among the sequences of BST-1, CD38, and Aplysia cyclase, and hence this substrate recognition mode and catalytic scheme appear to be common in the cyclase family.

PubMed: 11866528
DOI: 10.1006/jmbi.2001.5386

実験手法

X-RAY DIFFRACTION (2.4 Å)